Interleukin 2 receptor expression and interleukin 2 localisation in human solid tumor cells in situ and in vitro: evidence for a direct role in the regulation of tumour cell proliferation.

Frozen sections of 52 human solid tumours (38 malignant and 14 benign) of varied histogenesis were immunohistochemically stained with well characterised monoclonal antibodies (MAbs) to human interleukin 2 (IL-2) and the alpha and beta chains of its receptor (R). In all malignant specimens, the tumour cells expressed the IL-2R beta subunit (p75) but not the IL-2R alpha subunit (CD25). In 36 of 38 malignant tumours examined, there was conspicuous staining for IL-2 in the tumour cell nuclei/nucleoli and perinuclear cytoplasm. In the human solid tumour cell lines G361 (melanoma), A549 (lung), MCF-7 (breast) and WiDR (colorectal), both subunits of the IL-2R appeared to be expressed, although the alpha subunit only weakly. Exogenous addition of human recombinant (r) interleukin 2 altered cell numbers in 3 of the 4 cell lines (WiDR was refractory). When grown in the absence of exogenously added rIL-2, IL-2 staining was observed in all cell lines. The pattern of distribution was similar to that exhibited by the tumour cells in situ (i.e., a nuclear/nucleolar localisation). In G361 melanoma cells, this IL-2 staining was present in proliferating cells but disappeared as the cultures approached confluence. Addition of an IL-2R beta subunit blocking antibody to growing G361 cultures (grown in the absence of rIL-2) resulted in a significant reduction in cell numbers. We propose, therefore, that the presence of immunoreactive IL-2 and IL-2R expression is characteristic of human malignant cells and that IL-2 may play a role in the autocrine stimulation of proliferation of malignant cells, such as G361 melanoma cells.